Endothelin (ET) is a potent vasocontrictor peptide that induces characteristically long-lasting contractions. We used both intact and endothelium-denuded rat aortic rings to investigate the role of protein kinase C (PKC) in ET-induced contractions. ET (10-9) produced a gradual and sustained contraction of greater magnitude in denuded aortic rings than in intact rings. When aortic rings were pretreated with graded concentrations of different PKC inhibitors, ET-induced contractions were inhibited and the reduction was greater in intact than in denuded rings. Pretreatment of aortic rings with a PKC activator, potentiated ET- induced contractions. These results strongly suggest that PKC mediates ET-induced contractions in rat aortic rings, and that an intact endothelium is required for maximum inhibition by PKC inhibitors. ET also causes prostaglandin release. The mechanism remains unclear. Therefore, we pretreated rat aortic rings with either PKC activators or inhibitors and measured the release of prostacylin by radioimmunoassay. ET (10-9M) produced a 10-fold increase inprostacyclin release. Pretreatment with 10-9M of three different PKC inhibitors blocked ET induced prostacyclin release. ET induced prostacyclin release was also blocked by pretreatment with inhibitors of either phospholipase A2 or cyclooxygenase.